[unreadable] The underlying cellular and neurochemical mechanisms by which drugs modify the brain are a critical target of research designed to provide potential treatment strategies for addicted patients. Our hypothesis is that an essential component of addiction is aberrant glutamatergic neuronal plasticity, involving mechanisms common to LTP and LTD. This proposal will test this hypothesis by determining the effect of repeated amphetamine on glutamate receptor trafficking in the nucleus accumbens, a brain region critical for the expression of sensitization to drugs of abuse, and characerizing glutamatergic/cholinergic interactions in the ventral tegmental area, a region critical in the development of sensitization. We propose to investigate glutamate receptor and choline transporter trafficking at the cellular level, and investigate the cholinergic regulation of ventral tegmental excitability using in vivo microdialysis. Together, these approaches will provide a mechanistic link between drug-induced biochemical alterations and glutamatergic neuroplasticity, and will provide biochemical and neurochemical insight into the critical role of the cholinergic system in the regulation of midbrain excitability, and the consequences of aberrant regulation elicited by drugs of abuse. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]